I have previously established that antisera directed against immunoglobulin (Ig) heavy chains can produce either complete or class-specific humoral immunosuppression in mice and that certain types of murine leukemia and myelomas can be controlled with these antisera when anti-Ig treatment is begun before the malignancy is contacted. I now propose to further investigate the phenomenon of Anti-Ig immunosuppression from two standpoints. 1. Several aspects of the basic mechanism (mode of action) by which anti-Ig antisera interact with lymphocytes will be examined. Possible cytotoxicity will be determined by an in vitro complement-dependent assay. Reversibility of suppression will be evaluated by observing suppressed cells transferred into irradiated recipients. Congenitally athymic (nude) mice will be utilized to examine both the thymus dependency of escape from suppression and potential provision of the "second signal" to B cells necessary for antibody production. Lymphocyte stimulation resulting from minimal exposure to anti-Ig sera will be characterized as to conditions required for stimulation and the nature of aberrant products from stimulated cells. 2. Class-specific anti-Ig immunosuppression will be used to develop two models having significance for human clinical medicine. Thus heavy chain specific antisera (anti-micron, anti-gamma, anti-alpha, and anti-e) will be used in studies of reaginic antibody (IgE) control and myeloma control in animals already expressing actively growing myelomas at the time anti-Ig treatment is begun.